This project involves two goals: (1) Development of simple tests for detection of chemical abnormalities, suitable for the dried spots of blood already collected from newborn infants to screen for phenylketonuria and other inborn errors of metabolism by methods devised by this laboratory. (2) Search for new inborn errors of metabolism among developmentally disabled subjects whose family history suggests an autosomal recessive mode of inheritance of the disorder. Methods used emphasize use of bacterial inhibition assays, bacterial auxotrophs and special mutants, as well as paper, thin-layer, gas and liquid chromatographic procedure. Recent tests developed include a bacterial inhibition assay for uracil, which appears very promising as a urine test to detect any of several different inborn errors of the urea cycle that lead to increased production of pyrimidines. Another bacterial inhibition assay for blood elevations in glutamine is under study as a possible screening test for hyperammonemia, in which glutamic acid is converted to glutamine. Combined gas chromatography, mass spectrometry and computer techniques (made available by collaboration with other laboratories) appear to indicate a new inborn error of metabolism of dicarboxylic organic acids. Studies on a practical cord blood screening approach for Type II hyperbetalipoproteinemia include a nystatin yeast inhibition assay & a colorimetric determination for cholesterol. For the Beta-lipoprotein, the radial immunoassay and the enzyme-linked immunosorbant assay (ELISA) principles are under study. BIBLIOGRAPHIC REFERENCES: Naylor, E.W., Orfanos, A. and Guthrie, R. A Simple Screening Test for Arginase Deficiency (Hyperargininemia). J. Clin. Lab. Med. July, 1977, in press. Orfanos, A.P., Murphey, W.H. and Guthrie, R. A Simple Fluorometric Assay of Protoporphyrin in Erythrocytes (EPP) as a Screening Test for Lead Poisoning. J. Lab. Clin. Med. May, 1977, in press.